Is ACTC1 p.Ala146= (c.438T>C) pathogenic?

ACTC1 p.Ala146= (c.438T>C) is classified Likely benign in ACTC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-09). Ultra-rare (popmax 0.0165%, mid); Associated with dilated cardiomyopathy 1R.

What condition is associated with ACTC1 p.Ala146= (c.438T>C)?

ACTC1 p.Ala146= (c.438T>C) is associated with dilated cardiomyopathy 1R, hypertrophic cardiomyopathy 11, atrial septal defect 5 (ClinVar).

How common is ACTC1 p.Ala146= (c.438T>C) in the general population?

ACTC1 p.Ala146= (c.438T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ACTC1 p.Ala146=

c.438T>C · rs1238372620 · VCV2447971

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

dilated cardiomyopathy 1R

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.84	GERP -4.1, phastCons 0.97
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Overall 0.000137% 2/1,461,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
South Asian	0.0011%	91,076

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACTC1
Protein: p.Ala146=
Coding: c.438T>C
dbSNP: rs1238372620
Type: single nucleotide variant
Location: chr15:34793261 (GRCh38)

Full ACTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1R — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 11 atrial septal defect 5

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/actc1-p-ala146 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown